Resting metabolic connectivity in prodromal Alzheimer’s disease. A European Alzheimer Disease Consortium (EADC) project Silvia Morbelli a, *, Alex Drzezga b , Robert Perneczky c , Giovanni B. Frisoni d , Anna Caroli d,e , Bart N.M. van Berckel f , Rik Ossenkoppele f , Eric Guedj g , Mira Didic h , Andrea Brugnolo i , Gianmario Sambuceti a , Marco Pagani j,k , Eric Salmon l , Flavio Nobili i a Nuclear Medicine Unit, Department of Internal Medicine, San Martino University Hospital, Genoa, Italy b Department of Nuclear Medicine, Technische Universität München, Munich, Germany c Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany d LENITEM Laboratory of Epidemiology and Neuroimaging - IRCCS S. Giovanni di Dio-FBF, Brescia, Italy e Medical Imaging Unit, Biomedical Engineering Department, Mario Negri Institute for Pharmacological Research, Bergamo, Italy f Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, the Netherlands g Service Central de Biophysique et de Médecine Nucléaire and Centre Européen de Recherche en Imagerie Médicale (CERIMED), Assistance Publique des Hôpitaux de Marseille, Faculté de Médecine, Université de la Méditerranée, INSERM, Marseille, France h Service de Neurologie et de Neuropsychologie, Pôle de neurosciences cliniques, Assistance Publique des Hôpitaux de Marseille, Hôpitaux de la Timone, INSERM U751, Faculté de Médecine, Université de la Méditerranée, Marseille, France i Clinical Neurophysiology Unit, Department of Neuroscience, Ophthalmology and Genetics, San Martino University Hospital, Genoa, Italy j Institute of Cognitive Sciences and Technologies, CNR, Rome, Italy k Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden l Cognitive and Behavioral Neuroscience Centre, University of Liège, Liège, Belgium Received 10 September 2011; received in revised form 9 January 2012; accepted 12 January 2012 Abstract We explored resting-state metabolic connectivity in prodromal Alzheimer’s disease (pAD) patients and in healthy controls (CTR), through a voxel-wise interregional correlation analysis of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) by means of statistical parametric mapping. Baseline 18F-fluorodeoxyglucose-positron emission tomography of 36 patients with amnestic mild cognitive impairment who converted to Alzheimer’s disease (AD) dementia after an average time of 2 years (pAD) and of 105 CTR were processed. The area of hypometabolism in pAD showed less metabolic connectivity in patients than in CTR (autocorrelation and correlation with large temporal and frontal areas, respectively). pAD patients showed limited correlation even in selected nonhypometabolic areas, including the hippocampi and the dorsolateral prefrontal cortex (DLFC). On the contrary, in CTR group correlation was highlighted between hippocampi and precuneus/posterior cingulate and frontal cortex, and between dorsolateral prefrontal cortex and caudate nuclei and parietal cortex. The reduced metabolic connections both in hypometabolic and nonhypometabolic areas in pAD patients suggest that metabolic disconnection (reflecting early diaschisis) may antedate remote hypometabolism (early sign of synaptic degeneration). © 2012 Elsevier Inc. All rights reserved. Keywords: Prodromal Alzheimer’s disease; Positron emission tomography; Functional connectivity 1. Introduction The human brain is anatomically and functionally orga- nized into complex networks allowing both segregation and integration of information. Multidisciplinary research in neuroimaging has provided methods capable of exploring in vivo and noninvasively functional connectivity of these * Corresponding author at: Nuclear Medicine Unit, San Martino Univer- sity Hospital, Largo R. Benzi 10, 16132 Genoa, Italy. Tel.: +39 0105552029; fax: +39 0105556911. E-mail address: silviadaniela.morbelli@hsanmartino.it (S. Morbelli). Neurobiology of Aging xx (2012) xxx www.elsevier.com/locate/neuaging 0197-4580/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2012.01.005